Zijiang CHEN (China)
Prof. Chen focuses on reproductive endocrinology, reproductive genetics and assisted reproductive technology: PCOS, POF/POI, RSA, IVF/ICSI, PGD/PGS, etc. She has more than 300 publications on journals such as NEJM, Lancet, Cell, Nat Genet, JCI, PNAS, Cell Reasearch, Am J Hum Genet, Nat Commun, Hum Reprod Update, Fertil Steril, Hum Reprod, etc.
Prof. Chen serves as Assistant Secretary General of International Federation of Fertility Societies (IFFS), Executive Member of Asia Pacific Initiative on Reproduction(ASPIRE, 2014-2016), Board Member of Preimplantation Genetic Diagnosis International Society (PGDIS), Board Member of PGDSIG at ASRM, Director of Chinese Gynecological Endocrinology of OB/GYN Society.
Contributions to the Journals including Associate Editor: Human Reproduction Update, Gynecologic and Obstetric Investigation; International Consultant: American Journal of Obstetrics and Gynecology; Editorial Board Member: Asia Journal of Andrology; Guest Editor: British Journal of Obstetrics and Gynaecology; Deputy Editor-in-Chief: Chinese Journal of Obstetrics and Gynecology(Chinese), etc.
Abstract
Mitochondrial Replacement by Pre-Pronuclear or Polar Body Transfer in Human Embryos
Mitochondria are membrane bound organelles contain a small amount of DNA that is maternally inherited. Mutations in the mitochondrial DNA (mtDNA) can cause a range of diseases with severe clinical symptoms. It is estimated that at least 1 in 10,000 adults has clinically manifest mitochondrial disease. There has been limited success in developing effective treatments. Because mtDNA mutations are inherited from mother to children, replacement of defective mitochondria with nonpathogenic mtDNA provided by normal donor oocytes could be an effective approach. Transmission of disease-causing mitochondria could obviate the presence of mutant mitochondria in offspring. In 2015, UK became the first country to legalize mitochondrial replacement therapy (MRT). In 2016, the world’s first baby was born from MRT in Mexico.
Mitochon drial rep lacement techniques mainly include maternal spindle transfer (MST), pre-pronuclear transfer (PPNT), pronuclear transfer (PNT) and polar body transfer (PBT). In MST, PNT and PBT, cytoskeleton inhibitors like cytochalasin B is necessary, the safety of which in human embryo-related manipulation has not been rigorously evaluated. In our study, we showed a novel technique, in which female pre-pronucleus (PPN) can be isolated shortly after fertilization in a condition without cytoskeleton disruptors and then be successfully used for MRT, leading to the generation of human embryonic stem cell (ESC) lines with mtDNA carryover at very low levels. Importantly, mtDNA carryover didn’t increase during ESC culture and differentiation. Thereafter, on the basis of PPNT, we then reported the improved method of second polar body transfer (PB2T). The method doesn’t require cytoskeleton inhibitor as well. Moreover, it is easier to distinguish female and male pronuclei by removal of PPN and extruding PB2 comparing to removal of female pronucleus in previous PB2T combined with pronuclear transfer protocol. Normal human ESCs can be efficiently generated from reconstructed embryos by PB transfer (PBT). Importantly, mitochondrial DNA (mtDNA) carryover remains at low levels during subsequent ESC culture and differentiation.